Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling
Open accessPublished version of a preprint
Abstract
Insulin secretory granule (ISG) maturation is a crucial aspect of insulin secretion and glucose homeostasis. The regulation of this maturation remains poorly understood, especially how secretory stimuli affect ISG maturity and subcellular localization. In this study, we used soft X-tomography (SXT) to quantitatively map ISG morphology, density, and location in single INS-1E and mouse pancreatic β-cells under the effect of various secretory stimuli. We found that the activation of glucokinase (GK), gastric inhibitory polypeptide receptor (GIPR), glucagon-like peptide-1 receptor (GLP-1R), and G-protein coupled receptor 40 (GPR40) promote ISG maturation. Each stimulus induces unique structural remodeling in ISGs, by altering size and density, depending on the specific signaling cascades activated. These distinct ISG subpopulations mobilize and redistribute in the cell altering overall cellular structural organization. Our results provide insight into how current diabetes and obesity therapies impact ISG maturation and may inform the development of future treatments that target maturation specifically.
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Cites
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- Authors
- Deshmukh, A., Chang, K., Cuala, J., Hernandez Campos, M. J., Mahmood, S., Verma, R., Georgia, S., Loconte, V., & White, K. L.
- Affiliations
- University of Southern California (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- White, Kate L.
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2025-11
- Volume
- 33
- Issue
- 11
- Pages
- 1831-1843.e4
- ISSN
- 0969-2126 (ISSN-L)
- PMC
- PMC12435921
- OpenAlex
- W4413683713
- Cited by
- 9
- References
- 5
- Citations by year
- 2026: 7 · 2025: 2
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Structure (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion, cc-by-nc-nd)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (R35GM154893)
- National Institute of General Medical Sciences (P30GM138441)
- Biological and Environmental Research (DE-AC02-05CH11231)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- insulin secretion, pancreatic beta cells, glucokinase, GLP-1 receptor, GPR40, INS-1E cells, soft X-ray tomography
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